We have studied the biosynthesis of the insulin receptor in human IM-9 lymphocytes as well as in isolated rat adipose cells. The receptors were labeled by either biosynthetic incorporation of radioactive amino acids and sugars or by cell surface techniques. In addition, in order to identify the subcellular sites responsible for the biosynthetic processing of the receptor subcellular fractions enriched in endoplasmic reticulum, Golgi apparatus, and plasma membranes were prepared from rat adipose cells. This insulin receptor appears to be synthesized in the endoplasmic reticulum as a Mr=190,000 high mannose precursor. Processing of the precursor to yield the major subunits Mr=135,000 and 95,000 involves two steps. First, cleavage of the protein to generate the smaller subunits and second, terminal glycosylation to complete some of the high mannose chains to the complex type. In addition, some of the precursor appears to escape proteolytic cleavage but undergoes full processing of the carbohydrate chains and generates the Mr=210,000 component which is inserted in the plasma membrane. Both processing events occur probably in a distal Golgi vesicle during the transfer of the receptor to the plasma membrane.